Effects of exercise-based home pulmonary rehabilitation on patients with chronic obstructive pulmonary disease: An overview of systematic review

Background Clinical research on exercise-based home pulmonary rehabilitation (HPR) effectiveness in chronic obstructive pulmonary disease (COPD) treatment is rising, as are associated systematic reviews/meta-analyses (SRs/MAs). However, different SRs/MAs vary in outcome indicators, analysis methodologies, literature quality, and findings. This overview aimed to describe the findings of these SRs/MAs and assess their methodological quality. Methods From inception until April 2022, we searched PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan Fang. Two researchers searched these SRs/MAs separately, collected the data, and cross-checked it using predetermined rules. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) was used to evaluate the methodological quality of each contained SR/MA. The evidence was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 (PRISMA-2009). The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the validity of the results. Results A total of 433 records were found, with 44 chosen for full-text review. There were 11 SRs/MAs that matched the inclusion criteria. Our overview included studies published from 2010 to 2022. According to the AMSTAR 2 tool, one had low methodological quality, while the other 10 SRs/MAs had very low quality. The PRISMA statement revealed a low rate of complete reporting for eight items. The GRADE tool, on the other hand, revealed that the evidence quality for most outcomes was very low to moderate. Conclusion According to current research, exercise-based HPR may benefit COPD patients. Nevertheless, this finding is restricted by the low quality of the included SRs/MAs. And more high-quality and large-sample studies are needed in the future. Prospero ID: CRD42022322768. https://www.crd.york.ac.uk/prospero/#recordDetails

quality, with varying findings and limitations. Therefore, it is necessary to summarize these SRs/MAs.
A systematic review overview aims to compare, summarize, and synthesize results from several SRs/MAs [19]. Overviews benefit decision-makers by synthesizing the findings of the included studies and providing them with readily available evidence [20]. Therefore, the goal of this overview was to synthesize information from SRs/MAs to summarize the implications of home-based PR for COPD patients.

Methods
We followed the PRISMA statement [21], the Cochrane Handbook [22], and the PRIOR statement [23]. This overview was registered with PROSPERO (no. CRD42022322768).

Search strategy
The included studies were available in Chinese or English only. We systematically searched PubMed, Web of Science, Cochrane Library, Embase, CNKI, and Wan Fang databases from inception to April 2022. The following keywords were used: exercise, pulmonary rehabilitation, home, COPD, and meta-analysis. In addition, we carefully checked the references of all included research to confirm that the search was comprehensive. S1 Table contains the detailed search tactics and steps.

Inclusion and exclusion criteria 2.2.1. Inclusion criteria.
(1) Types of Included Reviews SRs/MAs are based on randomized controlled trials (RCTs) or non-randomized controlled trials (non-RCTs), with or without meta-analysis.
(2) Participants Adults diagnosed with chronic obstructive pulmonary disease (mild to very severe) were selected. The diagnostic criteria are based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [1], the European Respiratory Society [24], the American Thoracic Society [25], and the British Thoracic Society [26]. (

3) Interventions
The interventions refer to exercise-based home pulmonary rehabilitation, with/without usual care, such as walking, running, aerobic training, endurance training, resistance training, interval training, upper or lower limb training, etc.
(4) Comparators The comparator was usual care, no treatment, or in/outpatient exercise-based pulmonary rehabilitation.

Literature selection
Two authors used a predefined standardized search technique to search the database. All search results were integrated into Endnote X9 software to eliminate duplicate content. Two authors examined the title and abstract independently and excluded literature that did not fit the literature's inclusion and exclusion criteria. The full text was then read again to identify the final literature that would be included. A third author served as a judge to resolve any differences.

Data extraction
Based on a predesigned Excel spreadsheet, two authors extracted information separately. The information extraction included first author, publication year, type and the number of included studies, participants, interventions, comparisons, outcomes, tools for methodological quality assessment, and critical findings. A third author acted as a referee to resolve any disagreements.

Review quality assessment
Two authors evaluated the included SRs/MAs in the study separately. After concluding the evaluation, two authors double-checked the results. A third author served as a judge to resolve any differences.
The methodological quality of the included SRs/MAs was assessed using the AMSTAR-2 instrument [27]. There are 16 items in total, seven of which are crucial. Each item was given a "yes," "partial yes," "no," or "not conducted". Ultimately, the quality of each SR/MA was graded (four levels of high, medium, low, or very low) according to seven critical items.
The quality of each SR/MA report was assessed using the PRISMA checklist [28]. It consists of 27 elements that focus on each SR/MA's reported methods and outcomes. "Yes," "partial yes," or "no" were used to respond to each item. Each item's ultimate completion was reported as a ratio.
The GRADE [29] was used to assess the quality of the primary outcomes of the SRs/MAs included in the overview. Five key elements (limitations, inconsistency, indirectness, imprecision, and publication bias) were used to divide the quality of evidence into four grades (high, moderate, low, and very low).

Overlap calculation
The degree of duplication of the original literature for SRs/MAs was assessed by creating citation matrices for SRs/MAs and calculating the "corrected covered area" (CCA) [30]. The formula was calculated as CCA = (n-r)/(rc-r), where "n" is all original studies included in SRs/ MAs, "r" is all original studies included in SRs/MAs after de-duplication, and "c" is the number of studies included in the overview this time. The calculation result "0-5" indicates slight overlap, "6-10" indicates moderate overlap, "11-15" indicates high overlap, and ">15" indicates very high overlap.

Search results
433 published studies were discovered through the database search, with 175 repeated studies removed. A total of 214 publications were eliminated after reviewing the titles and abstracts. The full papers of 44 articles were downloaded when they were deemed eligible. Thirty-three papers were excluded after a full-text examination. Ultimately, this overview contained 11 SRs/ MAs. Fig 1 shows the study screening process. S2 Table shows a list of excluded publications and the grounds for their exclusion.

Features of included studies
The detailed features of each of those SRs/MAs are summarized in Table 1. The SRs/MAs in this overview were published between 2010 and 2022. There were 11 SRs/MAs in all, seven in

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Pulmonary rehabilitation and chronic obstructive pulmonary disease English and four in Chinese. The total number of participants in SRs/MAs ranged from 464 to 2352, and the number of RCTs ranged from 9 to 23. For methodological quality assessment, seven articles used the Cochrane Risk of Bias instrument, one used the Jadad scale, one used the PEDro scale, one used the Quality Assessment Tool for Quantitative Studies, and the other article did not mention any particular tool. The intervention group used exercise-based home pulmonary rehabilitation, including endurance exercise training, aerobic training, strength training, breathing gymnastics, etc. HPR based on activity was typically four weeks or longer, two sessions per week or more, and at least 30 minutes per session. The control group received usual care, conventional medication, no intervention, or outpatient/inpatient PR. Of the 11 included studies, six compared exercise-based HPR with usual care, standard medical care, or no intervention [32-35, 38, 40], three compared exercise-based HPR with outpatient or center-based PR [36,37,39] and two included both comparisons [16,31].   Table 2 shows the methodological quality assessment results of the included reviews. Of the 11 SRs/MAs, only one systematic review [16] was judged to be of low quality, and the quality of the other studies was assessed as very low. The AMSTAR 2 tool's emphasis items are 2, 4, 7, 9, 11, 13, and 15. For item 2, four studies [16,36,39,40] offered a protocol registration or publication before commencement. For item 4, only four included studies [16,36,39,40] showed the adoption of a specific search strategy. Regarding item 7, only one study [36] supplied a list of eliminated documents and the reasons for their exclusion. For item 9, ten reviews [16,31,[33][34][35][36][37][38][39][40] evaluated the risk of bias in every study with appropriate tools. For item 11, nine [16,[33][34][35][36][37][38][39][40] analyzed the data statistically using relevant procedures, and one study [31] used narrative SR without quantitative analysis. For item 13, only one study [16] considered the risk of bias when presenting the findings. Regarding item 15, two studies [16,38] considered publication bias in interpreting or discussing the results. Furthermore, none of the researchers stated why the study was chosen nor indicated the funding sources for the included study.

Report quality
The percentage of included studies that met each of the 27 PRISMA criteria for transparent reporting is shown in Fig 2. Seventeen out of 27 items were adequately reported, over 70%. The objectives and synthesis of results were reported adequately (100%). The abstract was written inadequately (0%). In the section on methods, Q5 (protocol and registration), Q8 (search), and Q16 (additional analyses) reported incomplete (�50%); Q22 (risk of bias across studies), and Q23 (additional analyses) in the results section were not adequately described (�50%); insufficient detail in the description of Q27 (funding) (27%). Overall, two SRs/MAs [16,39] reached over 85% compliance. The specific evaluation content is shown in S4 Table.

Quality of evidence for relevant outcomes
The quality of evidence for all results varies from very low to moderate. No outcome was categorized as high quality. Vieira's study [31] had only qualitative analysis results and could not be assessed for the quality of evidence. Ten SRs/MAs [16,[32][33][34][35][36][37][38][39][40] included 71 outcomes. Of these outcome indicators, 12 were of moderate quality, 17 were of low quality, and 38 were of very low quality. The main causes for demotion were the limitations of the original research, followed by imprecision, publication bias, and inconsistency. S5 Table shows the GRADE evaluation in detail.

HPR versus control groups (usual care, standard medical care, or no intervention).
(1) HRQoL Eight reviews [16, 31-35, 38, 40] reported that exercise-based HPR has the potential to improve overall HRQoL compared to control groups. The strongest evidence (moderate) comes from Neves [16], which describes that exercise-based HPR improved the CRQ fatigue scores of subjects in the intervention group. Five included studies [16,[32][33][34][35] used the total score of CRQ to assess HRQoL after intervention. The results showed that the CRQ total scores of COPD patients in the HPR group were significantly higher than that in the control group, and the difference was statistically significant. The analysis results of the five included studies [16,[33][34][35]38] showed that after the intervention, the SGRQ score of the HPR group was significantly improved, and the HRQoL was improved.
(3) Dyspnea The effects of HPR on dyspnea were reported in seven studies [16,[31][32][33][34][35]40]. In three reviews on measuring dyspnea with Borg score [33][34][35], meta-analysis results showed that after intervention, the dyspnea score of the HPR group was lower than that of the control group. The medium-quality study [40] found that the CRQ Dyspnea score of the HPR group had statistically significant improvement, but there was no clinically significant improvement. According to the evidence from four SRs/MAs [16,[32][33][34], participants who received the intervention exhibited considerable improvement assessed by CRQ-Dyspnea. The study with the highest quality [16] used MRC to evaluate the dyspnea of the two groups of subjects. The results showed that although the MRC score of the HPR group was significantly lower than that of the control group after the intervention, the difference was not statistically significant.
(4) Pulmonary function Three reviews [33,35,38] reported the pulmonary function of the two groups of subjects after intervention. Liu's study [33] indicated that HPR seems to have some sound effects on increasing pulmonary function in COPD patients, according to FEV1/FVC assessments. Li's MAs [35] showed that HPR is ineffective in increasing pulmonary function in individuals with stable COPD. According to Fu's MAs [38], compared with the control group, the main indicators of pulmonary function of stable COPD patients receiving exercise-based HPR treatment have significantly improved, with statistically significant differences.
(2) Exercise capacity Five reviews [16,31,36,37,39] reported that exercise-based HPR has similar effects on exercise capacity compared to OPR. Moderate quality evidence [39] showed no significant difference in the 6MWT/6MWD data between HPR and OPR. One study [37] reported similar EWST results between exercise-based HPR and center-based PR.
(3) Dyspnea According to the meta-analysis findings, there is no difference between exercise-based home or community pulmonary rehabilitation and OPR [16,31,36,37,39]. A comparison of HPR and OPR showed no difference in CRQ-dyspnea scores [16,36,37,39]. The meta-analysis did not find a difference in mMRC scores between the HPR and OPR groups [37,39].

Discussion
This overview of systematic reviews was intended to summarize the key features and evaluate the quality of evidence from selected SRs/MAs about the efficacy of exercise-based HPR in COPD.

Evidence quality summary
Although almost all included SRs/MAs have come to positive conclusions that there is substantial evidence that HPR is helpful, the quality of the evidence is inadequate to draw strong judgments. The overall methodological and statistical presentation quality of these included studies were typically low, according to the AMSTAR-2, PRISMA, and GRADE appraisal results. This overview applied AMSTAR-2 to evaluate the methodological quality of selected SRs/ MAs. Most researchers lacked a clear presentation and explanation of preregistration study processes, thorough search methodologies, and reasons for excluding literature. This could undermine the transparency of the studies that were included, as well as the dependability of the results. None of the 11 SRs/MAs indicated why certain types of studies were included, making it difficult to guarantee that reasonable inclusion criteria were met. The source of funding of original studies was not reported by all eleven reviews, which may affect the reliability due to potential conflicts of interest. In addition, the included SRs/MAs have flaws such as the risk of bias, heterogeneity, and publication bias, all of which impair the validity of the evidence quality. Except for one study whose methodological quality was low, most of the included reviews were extremely low, according to AMSTAR-2. The above problems should be addressed in future research.
The included reviews were of average quality, according to the PRISMA tool. The structured summary, protocol and registration, search strategy, additional analyses, risk of bias across studies, and funding details were standard low-scoring criteria. The results showed that items 4, 7, 9, 11-14, 17-18, 20-21, and 24 provided sufficient descriptions, but the rest received poor ratings. As a result, future research should adhere to PRISMA guidelines.
This study used the GRADE evaluation tool to rate the level of evidence for the outcome indicators included in the literature, with most indicators having a very low to moderate level of evidence. The main reason for the downgrading of the evaluation was study limitations, mainly in the implementation of randomization, blinding, and allocation concealment schemes in the original study were imperfect. This may be due to the characteristics of the intervention, which makes it difficult to achieve blinding of patients and investigators, and future clinical studies should further improve their methodological quality. The second is the large heterogeneity among the original studies, which directly reduces the reliability of the evidence. This needs to be addressed with further clarification of inclusion and exclusion criteria and appropriate subgroup analysis. Meanwhile, some included literature had more serious problems of imprecision and publication bias. Some Chinese literature included a small sample of studies, and some studies were not analyzed for publication bias, with some risk of publication bias. All of the above factors can lead to discrepancies between study findings and the actual situation, which means that more high-quality randomized controlled studies are needed to provide reliable data.

Summary of major discoveries
Most of the included studies [16, 31-35, 38, 40] suggested that HPR improves HRQoL and exercise capacity and relieves dyspnea symptoms compared to COPD patients who had usual care or regular medical treatment. COPD patients may experience peripheral muscle dysfunction, dyspnea, decreased exercise tolerance, and a lower HRQoL [41]. Changes in daily life activities in COPD patients correspond to improvements in HRQoL. The positive changes in these outcome indicators may be because that HPR increases the skeletal muscle strength of patients and can sustain change in their health behaviors [33]. Additionally, none of the incorporated SRs/MAs recorded adverse events in patients receiving exercise-based HPR, which appears safe for COPD patients. However, we cannot confirm whether HPR significantly affects pulmonary function, possibly because only three studies [33,35,38] included pulmonary function metrics. Further research into the effect of HPR intervention on pulmonary function in COPD patients is still needed.
Compared to OPR, HPR does not have worse outcomes. In terms of improving HRQoL, exercise capacity, and relieving symptoms of dyspnea, these studies [16,31,36,37,39] confirmed that HPR and OPR have similar effects. The main drawback of OPR is its limited availability. Patient-related barriers include travel and transportation to rehabilitation centers, inconvenient hours, weather factors, illness, and disruptions to established routines [42]. A qualitative study found that participants were more comfortable with pulmonary rehabilitation in a home setting than in a hospital or center [43]. Most participants felt that HPR was able to overcome the barriers of OPR while gaining support from groups such as friends, family, and neighbors. Therefore, HPR is more flexible and convenient, making it a viable alternative for some patients who are unwilling or unable to participate in hospital or outpatient rehabilitation programs.

Suggestions for future research
Although HPR may have short-term efficacy in COPD patients, the current analysis found no evidence of long-term efficacy of exercise-based HPR. We recommend that future RCTs be designed with extended follow-up to determine the long-term clinical effectiveness of HPR. At the same time, to minimize bias as much as feasible, we recommend that subgroup analysis of SR/MA adhere to a consistent intervention, duration and follow-up, and outcome assessments. HPR as an alternative format, appears to be safe and feasible, but further research should be done to determine the effects of home-based pulmonary rehabilitation on other outcomes.
HPR is less expensive in terms of time and space but has similar costs to OPR in terms of professional guidance and medical examinations [44]. It has not been possible to determine the economic differences between the two [45]. Future studies should also consider the financial costs of home pulmonary rehabilitation, including health services and individual costs, which require a comprehensive economic analysis of the costs and benefits to patients and health systems.
We recommend that future trials be adequately randomized and concealed, with the blinding of outcome assessors and statistical analysts. Minimized knowledge of which patients received the trial intervention and which patients received the control intervention in the clinical study. The monitoring mechanism is also improved so that the study designer is not involved in the implementation of the trial and does not have direct contact with patients, thus reducing the impact of bias on the study. It is also recommended that researchers report as completely as possible in the blinded and allocation concealment implementation of the study.

Limitations
First, there may be some duplicate original papers in the enrolled reviews. Although we briefly describe the overlap of articles in the included SRs/MAs, we did not explore these overlaps systematically. As a result, this may lead to inaccurate data reporting. Second, the AMSTAR-2, PRISMA, and GRADE assessment is a subjective process. There is no guarantee of the accuracy of the assessor's assessment. Third, we only focused on a few outcomes, which may not reflect HPR's combined efficacy in COPD. Fourth, due to linguistic constraints, we included SRs/MAs covering only Chinese and English literature, and the search may not have been comprehensive. In addition, we recommend that the monitoring mechanisms be improved so that researchers report as completely as possible in the blinded and allocation concealment implementation of the study.

Conclusions
This overview of SRs/MAs suggests that exercise-based HPR may positively affect COPD. Moreover, these meta-analysis results show that exercise-based HPR is not worse than outpatient/center-based PR, and from this standpoint, it may be an alternative to maintaining outpatient/center-based PR. However, these conclusions were restricted by the methodology, reporting quality, and evidence quality for all included SRs/MAs.